Effects of delayed administration of methohexital and ketamine on posthypoxic cell damage of primary neuronal cultures.

Primary neuronal cultures from chick embryo cerebral hemispheres received NaCN (cytotoxic hypoxia) for 120 min and were then allowed to recover. Methohexital (300 mumol/l) or ketamine (30 mumol/l) given either before or during the hypoxic period elevated adenosine triphosphate (ATP) content of the cultures 15 min after hypoxia. Prehypoxic administration of ketamine also preserved the structural integrity and ATP content of neurons 20 h later, while methohexital did not. Ketamine elevated ATP content as measured 20 h after hypoxia even when administered 15 min after beginning of recovery. Pharmacokinetic reasons for contradictory effects of ketamine on neuronal cell loss in vivo ischemia studies and our in vitro experiments are discussed.